Significance Some HIV-seronegative individuals, exposed to the virus through high-riskbehavior, were infected at a low level but had not developed the antibodies that signal the infection. This observation remains controversial. The SIV/monkey model can help to understand how silent or latent HIV infection is established. Objectives To confirm the hypothesis that a latent infection with SIV is established in transiently viremic monkeys. Results Transient viremia following intravaginal inoculation of SIV is characterized by intermittent virus isolation from PBMC only during the first weeks and by lack of seroconversion to SIV antigen. The incidence of transient viremia was common, occurring in 29 of 53 vaginally inoculated monkeys, usually in those monkeys inoculated with 1 or more ten-fold dilution of the challenge virus stock. One monkey, 20563, that had been SIV culture - negative for more than 1 yr, spontaneously became viremic again and this animal progressed over another 1.5 yrs to develop simian AIDS. At necropsy of the remaining transiently viremic monkeys, no infectious virus was isolated from lymphoid tissues or genital mucosa. However, SIV was detectable by sensitive, nested PCR in the PBMC and /or lymphoid tissues of 10 of 10 monkeys tested. In addition, viral RNA was detected by RT-PCR in some of the tissues from 4 of the 10 animals that were SIV-PCR positive. Immune responses to SIV in transiently viremic monkeys were characterized by very weak antibody responses detectable in a minority of monkeys only with enhanced chemiluminescence, weak cytotoxic T lymphocyte responses in 3 of 5 animals tested and lymphocyte proliferative responses to SIV proteins in a majority of the animals. Future Directions To reactivate SIV productive infection in transiently viremic monkeys with pharmacologic or immunologic interventions, and to determine the virulence of SIV recovered after reactivation by the inoculation of naive monkeys with infectious plasma. KEYWORDS SIV, pathogenesis